This invention relates to a therapeutic combination of compounds to provide analgesic activity.
For clinical purposes, pain can be categorized into three groups: (1) acute pain; (2) continuous pain in terminally ill patients; and (3) other forms of chronic pain. In acute pain, a specific noxious stimulant of limited duration can be identified.
An additional distinction that is relevant to chronic pain is the difference between pain caused by a tissue-damaging process that excites nociceptive afferents and pain caused by pathologic changes in nociceptive neurons (neuropathic pain). Nociception refers to the neural mechanisms by which noxious stimuli are detected.
Nociception involves two steps: transductions of noxious stimuli by peripheral nerve endings and transmission of these signals to the central nervous system. Neuropathic pain typically persists and may even have its onset long after the original causative stimulus has been removed.
There are many Drugs Useful for the Treatment of Pain which are known in the literature and to the skilled artisan. Oral combinations of aspirin with codeine or other narcotic analgesics are known to provide additive analgesic effects in man. The Pharmacological Basis of Therapeutics, 5th edition, Macmillan Publishing Co., 1975, pp. 325-358.
More active analgesic combinations are in constant demand because they offer the attractive possibility of relieving pain with reduced dosages, thereby diminishing the expected side effects and toxicity that would otherwise result from higher dosages. It would be particularly desirable to acquire a synergistic combination effect. Such a composition is the subject of the present invention.
The phenyl oxazole and phenyl thiazole compounds of the instant invention are useful for the treatment of neurodegeneration. Surprisingly, and in accordance with this invention, Applicants have discovered that these phenyl oxazoles and phenyl thiazoles can be useful for the treatment of pain and can provide a synergistic effect when administered with one or more other Drugs Useful in the Treatment of Pain. The combination could address a long felt need for a safe and effective treatment for pain.